In the context of the present application, the term turbid medium is to be understood to mean a substance consisting of a material having a high light scattering coefficient, such as for example an intralipid solution or biological tissue. The term light is to be understood to mean non-ionizing electromagnetic radiation, in particular with wavelengths in the range between 400 nm and 1400 nm.
In the past decades, optics of turbid media such as biological tissue has become a widespread field of research and has found clinical applications in for instance monitoring (e.g. pulse oxymeter), cosmetics (e.g. port wine stain removal), and cancer treatment (e.g. photo dynamic therapy). Several techniques for optical imaging of turbid media (in particular for imaging biological tissue) are known, e.g. Optical Coherence Tomography, Confocal Microscopy; Two-Photon Microscopy, and Diffuse Optical Tomography. In diffuse optical imaging, a measurement geometry comprising many source and detector positions for acquisition of 3-D tomographic images is possible, or e.g. a geometry with limited numbers of sources and detectors (such as in a hand-held probe) to provide a simple map of the object to be imaged or to read-out just one or more specific parameters. In these applications, typically visible light, NIR (near infra-red), and/or IR (infra-red) light is used and this light can be provided as a continuous wave, in form of pulses, or as photon density waves, for example. Also, several different techniques using monochromatic light, multi-wavelength light, or a continuous spectrum are known in the art. Further tissue inherent fluorescence or fluorescence of a fluorescent contrast agent can be exploited. These applications all benefit in one way or another from the spectral features which are present in tissue, as will be explained with reference to FIG. 1.
Absorption spectra of the main chromophores which are present in, for instance, breast tissue are shown in FIG. 1. In FIG. 1 showing the respective absorptions of the main chromophores as a function of wavelength, it can be seen that absorption properties of the main chromophores hemoglobin, oxy-hemoglobin, water, and lipid differ considerably in their dependency on the wavelength of incident light. It can further be seen that the spectra of these constituents do not show features of narrow optical bandwidth but rather only features having a considerably large bandwidth.
Spectroscopy on tissue allows exploiting the different spectral characteristics such that the chromophores of the tissue and hence the composition of the tissue can be identified and, if desired, visualized and/or analyzed. Promising examples relying on in vivo optical spectroscopy of diffuse light emanating from tissue include imaging of breast cancer (e.g. by diffuse optical tomography), fluorescence imaging (e.g. using inherent fluorescence or fluorescent contrast agents) and monitoring of diabetes. However, an inherent problem occurring in spectroscopy on turbid media such as tissue is that, due to the relatively high amount of inherent scattering of light in tissue, the light emanating from the turbid medium under examination is strongly attenuated and, even more important, is of diffuse nature. Light, once diffusive, cannot be collimated effectively and hence acquisition of an optical spectrum of light emanating from such a turbid medium is inefficient. This inefficiency is a problem which has to be overcome to improve the applicability of tissue optics. The reason for this inefficiency will be described in the following.
For understanding the collection inefficiency occurring in optical examination of turbid media, a closer look on the optical characteristics is necessary. The “etendue” G which is also called acceptance, throughput, light-grasp, or collecting power is a property of an optical system which characterizes how “spread out” the light is in area and angle. The etendue can be defined in several equivalent ways. From the source point of view, it is the area A of the source times the solid angle Ω the system's entrance pupil subtends as seen from the source, i.e. G=A Ω. This product is shown in FIG. 2. From the system point of view, the etendue is the area of the entrance pupil times the solid angle the source subtends as seen from the pupil. However, these definitions apply for infinitesimally small “elements” of area and solid angle and have to be summed over both the source and the diaphragm. A perfect optical system would produce an image with the same etendue as the source. In other words, in a perfect optical system, the etendue is conserved; in imperfect real systems however, the etendue usually gets worse (i.e. to higher values). The etendue is related to the Lagrange invariant and the Optical invariant.
In a system for optical examination of turbid media in which diffuse light is to be coupled into a spectrometer, the etendue (or collecting power) of the spectrometer is intrinsically much smaller than that of the diffuse source (which by its nature has an etendue close to the maximum possible). A conventional spectrometer relies on the narrow extent of a slit or pinhole to obtain sufficient spatial resolution on its detector, since the spatial resolution is subsequently translated into spectral resolution. Since the spectroscopy of diffuse light, as for example emanating from turbid media formed by biological tissue, is inherently inefficient due to the etendue mismatch described above, this seriously compromises detection threshold and sampling time. It has been found that this etendue problem can hardly be dealt with at the detector side. Making use of a large etendue detector would be preferable in view of the etendue mismatch. However, in conventional arrangements this is not possible in view of the required spectral resolution.
In principle, it would be advantageous to use a photo multiplier tube (PMT) as a detector in such devices since it is very sensitive (internal gain) and has a fast response (high bandwidth) combined with a large area (high etendue). However, using a photo multiplier tube (PMT) comes along with some problems such as a limited dynamic range and vulnerability to overexposure. Further, the sensitivity of a PMT drops significantly in the near infra-red (NIR) of the optical spectrum.
There are further constraints with respect to examination of living biological tissue. A white light source with high power and brightness is required to fulfill the maximum possible requirements with respect to measurement quality. If measurement time is an issue, a bright source is required. Extremely bright white light sources have become available based on supercontinuum generation using intense femtosecond light pulses propagating through a holey fiber. However, in biological tissue there is a so-called Maximum Permissible Exposure (MPE). For sub-second exposure in the near infrared at small spot size, this can be in the order of one Watt.
Recently, a new type of spectrometer has been invented, the “Matrix Spectrometer” based on Coded Aperture Imaging. It uses a technique called Multimodal Multiplex Spectroscopy (MMS), which employs a wide area aperture with an encoded mask to increase the light throughput by an order of magnitude, given the same spectral resolution. U.S. Pat. No. 7,301,625 B2 shows an aperture coded spectrometer for spectral characterization of diffuse sources. The slit of conventional spectrometers is replaced by a spatial filter or mask. Using a number of different masks is proposed.